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Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells
Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288720/ https://www.ncbi.nlm.nih.gov/pubmed/25569210 http://dx.doi.org/10.1371/journal.pntd.0003414 |
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author | Katawa, Gnatoulma Layland, Laura E. Debrah, Alex Y. von Horn, Charlotte Batsa, Linda Kwarteng, Alexander Arriens, Sandra W. Taylor, David Specht, Sabine Hoerauf, Achim Adjobimey, Tomabu |
author_facet | Katawa, Gnatoulma Layland, Laura E. Debrah, Alex Y. von Horn, Charlotte Batsa, Linda Kwarteng, Alexander Arriens, Sandra W. Taylor, David Specht, Sabine Hoerauf, Achim Adjobimey, Tomabu |
author_sort | Katawa, Gnatoulma |
collection | PubMed |
description | Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4(+) T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4(+)CD25(hi)Foxp3(+) regulatory T cells. These profiles included increased IL-17A(+), IL-4(+), RORC2(+) and GATA3(+)CD4(+) T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses, especially IL-13, were observed in vitro in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis. |
format | Online Article Text |
id | pubmed-4288720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42887202015-01-12 Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells Katawa, Gnatoulma Layland, Laura E. Debrah, Alex Y. von Horn, Charlotte Batsa, Linda Kwarteng, Alexander Arriens, Sandra W. Taylor, David Specht, Sabine Hoerauf, Achim Adjobimey, Tomabu PLoS Negl Trop Dis Research Article Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4(+) T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4(+)CD25(hi)Foxp3(+) regulatory T cells. These profiles included increased IL-17A(+), IL-4(+), RORC2(+) and GATA3(+)CD4(+) T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses, especially IL-13, were observed in vitro in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis. Public Library of Science 2015-01-08 /pmc/articles/PMC4288720/ /pubmed/25569210 http://dx.doi.org/10.1371/journal.pntd.0003414 Text en © 2015 Katawa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Katawa, Gnatoulma Layland, Laura E. Debrah, Alex Y. von Horn, Charlotte Batsa, Linda Kwarteng, Alexander Arriens, Sandra W. Taylor, David Specht, Sabine Hoerauf, Achim Adjobimey, Tomabu Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells |
title | Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells |
title_full | Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells |
title_fullStr | Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells |
title_full_unstemmed | Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells |
title_short | Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells |
title_sort | hyperreactive onchocerciasis is characterized by a combination of th17-th2 immune responses and reduced regulatory t cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288720/ https://www.ncbi.nlm.nih.gov/pubmed/25569210 http://dx.doi.org/10.1371/journal.pntd.0003414 |
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